Water → ethyl 5-chloro-6-{[(3R)-1-(4-fluorobenzyl)-3-pyrrolidinyl]amino}nicotinate

HRID 2376026Notes

Reaction equation

Cl.Cl.[F:3][C:4]1[CH:16]=[CH:15][C:7]([CH2:8][N:9]2[CH2:13][CH2:12][C@@H:11]([NH2:14])[CH2:10]2)=[CH:6][CH:5]=1.[CH2:17]([O:19][C:20](=[O:29])[C:21]1[CH:26]=[C:25]([Cl:27])[C:24](Cl)=[N:23][CH:22]=1)[CH3:18].C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C.CCOC(C)=O>[Cl:27][C:25]1[C:24]([NH:14][C@@H:11]2[CH2:12][CH2:13][N:9]([CH2:8][C:7]3[CH:6]=[CH:5][C:4]([F:3])=[CH:16][CH:15]=3)[CH2:10]2)=[N:23][CH:22]=[C:21]([CH:26]=1)[C:20]([O:19][CH2:17][CH3:18])=[O:29]

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of (3R)-1-(4-fluorobenzyl)-3-pyrrolidinamine dihydrochloride (3.5 g) in DMF (35 ml) was added 5,6-dichloronicotinic acid ethyl ester (3.38 ml) and K2CO3 (6.34 g), the mixture was stirred at 100° C. for 4 hours under N2 atmosphere. The mixed solution was poured into a mixture of water (250 ml) and AcOEt (250 ml). The organic layer was separated, washed with water twice and brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography eluted with AcOEt:hexane=1:2 to give ethyl 5-chloro-6-{[(3R)-1-(4-fluorobenzyl)-3-pyrrolidinyl]amino}nicotinate (3.75 g).

Workup

customThe organic layer was separated
washwashed with water twice
dry with materialbrine, dried over sodium sulfate
concentrationconcentrated in vacuo
customThe residue was purified by silica gel column chromatography
washeluted with AcOEt

Sources & evidence

ORD record: ord-037271096e8f4c6dbab4c2b479de9b30
Source dataset: uspto-grants-2008_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07465731B2

Reaction notes

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